Studies on the control of cholesterol biosynthesis in isolated hepatocytes will be continued. The effect of the state of cholesterol, whether in alcohol solution when added to the medium in lecithin-cholesterol dispersion, in "remnants" or in native lipoproteins, makes a great difference, but it is not clear why. The possible correlation between increases in the free and esterified content of various intrahepatic cholesterol-compartments and the activity of 3-hydroxy-3-methylglutaryl CoA reductase will be determined to gain additional information on the mechanism of the inhibition of cholesterol synthesis by dietary cholesterol. Effects of hormones, particularly insulin, glucagon and anterior pituitary hormones, on synthesis of the reductase in isolated hepatocytes will be studied. Hypocholesterolemic drugs, including Clofibrate and Halofenate will also be studied. BIBLIOGRAPHIC REFERENCES: Prevention of Cold Inactivation of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase by NADPH. Heller, Renu A. and Gould, R. Gordon. (1975) Biochim. Biophys. Acta 388, 254-259. Correlation of Rat Liver Chromatin-Bound Free Esterified Cholesterol with the Circadian Rhythm of Cholesterol Biosynthesis in the Rat. Erickson, Sandra K., Davison, Audrey M. and Gould, R. Gordon. (1975) Biochim. Biophys. Acta 409, 59-67.